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[FitEyes Discussion 17102] The Selenium Paradox in Glaucoma

Submitted by terry on Sat, 11/26/2016 - 3:20pm

David Wrote:

*One glaucoma mystery explained: why is selenium a risk factor?*

*A medical hypothesis*

In this paper I will present the selenium paradox and propose anexplanation. Furthermore, I will show that understanding the seleniumparadox helps us understand a number of other mysteries related toglaucoma. And I propose a new way to understand the glaucoma pathologythrough the lens of one carbon metabolism (what is also called themethylation cycle).

Selenium is an essential trace mineral humans must obtain from their diet.Humans require selenium for a number of selenium-dependent enzymes (whichare also called selenoproteins) [7].

Research has shown that higher levels of selenium in the blood, and to someextent higher levels of selenium in the aqueous humor, increase the risk ofglaucoma. A 2009 article in the British Journal of Ophthalmology [1]concluded, "our data, added to that of others, suggest that glaucoma isselenium-related."

So that's what the research says. The only problem is that it seems to be*paradoxical*. First, in the general sense, it is paradoxical becauseselenium is an antioxidant and glaucoma patients, who, as a class, haveelevated oxidative stress in eye tissues and aqueous humor, obviously needmore antioxidant support. Oxidative stress is composed of either/bothreduced functionality of antioxidants and elevated levels of oxidants(reactive oxygen species, etc.).

Oxidative stress is a serious problem for glaucoma patients. "Oxidativestress, occurring not only in the trabecular meshwork, but also in retinalcells, appears to be involved in the neuronal cell death affecting theoptic nerve in open angle glaucoma [2]."

A 2014 article in the journal Current Eye Research concludes, "Theseresults suggest that a significant increase in oxidative stress may play arole in the pathogenesis of primary open angle glaucoma and primary angleclosure glaucoma [4]." The same can be said of other forms of glaucoma.

In fact, FitEyes, with the help of Robert Ritch, MD, has been emphasizingthe following unified understanding of glaucoma since August 2010:

*All glaucomas have a final common pathway of retinal ganglion cell deathinvolving low-grade inflammation, oxidative damage, mitochondrialdysfunction, and glial hyperactivation.*

Even more specifically, studies have shown that glaucoma patients havereduced levels of the antioxidant *glutathione*. One study showed thatglutathione levels were decreased at the earliest stages of glaucoma [3].

"After correction for age and gender influences on blood glutathionelevels, patients with glaucoma exhibited significantly lower levels ofreduced and total glutathione than did matched control subjects [12]."

Glutathione is one of the most important antioxidants in the human body.Mark Hyman, MD, calls it the "mother of all antioxidants, the masterdetoxifier and maestro of the immune system [5]."

Glutathione peroxidase (GPx) is the general name of an enzyme family whosemain biological role is to protect the body from oxidative damage by makinguse of glutathione. The molecule glutathione and the enzyme glutathioneperoxidase are a system -- an antioxidant system.

Knowing the important of glutathione and it's deficiency in glaucoma, hereis the deeper paradox: glutathione peroxidase depends on *selenium*. It isbuilt on (contains) selenium. Without selenium, there is no glutathioneperoxidase -- and little or no antioxidant activity from the "mother of allantioxidants" in the human body.

Five selenium-containing glutathione peroxidases (GPx) have beenidentified: GPx1, GPx2, GPx3, and GPx4 have been shown to beselenium-containing enzymes in all mammals, while GPx6 is also aselenoprotein in humans [6].

Although each glutathione peroxidase is a distinct selenoprotein, they areall antioxidant enzymes. They all "reduce potentially damaging reactiveoxygen species (ROS), such as hydrogen peroxide and lipid hydroperoxides,to harmless products like water and alcohols by coupling their reductionwith the [transient] oxidation of glutathione [7]." In this process,glutathione disables to damaging oxidant (ROS).

Dietary selenium normally favorably affects plasma reduced glutathioneconcentrations [10]. So selenium supplementation should be beneficial forglaucoma. But it isn't. This is a paradox because it does not make sensethat something glaucoma patients need more of would be detrimental to them.

Now that we understand the paradox, let's attempt to resolve it. The basisfor this resolution is an understanding of the methylation cycle.

The methylation cycle is a term that is widely used today. But Dr. AmyYasko explains that it is actually a combination of four interrelatedbiochemical cycles, including:

Another name for the methylation cycle is "one-carbon metabolism". This isan even better name because methylation happens outside the four pathwayslisted above. It's almost ubiquitous. The name "one-carbon metabolism"comes from the fact that a methyl chemical group is a fundamentalone-carbon unit in biological systems. It consists of one carbon atom,three hydrogen atoms and a single available bond that can attach to othermolecules. When the methyl group (one carbon unit) is attached to amolecule, that is a methylation reaction.

The methylation cycle is directly or indirectly involved in the synthesisof biologically important compounds including:

Several of these substances are typically found to be low in glaucoma,leading some glaucoma specialists to recommend them as supplements.

The body makes insufficient quantities of these compounds because of apartial block in the methylation cycle. This leads to a general connectionbetween glaucoma and the methylation cycle. There may be more specificconnections, especially for glaucoma patients with certain SNP's (geneticpolymorphisms). (Side note: cysteine is the rate-limiting factor incellular glutathione biosynthesis, since this amino acid is relatively rarein foods.)

Furthermore, and of great interest in glaucoma, the methylation cycle (viaSAMe production) is required for the formation of *myelin* (the coveringfor nerves). But that subject is outside the scope of this paper.

Therefore, the methylation cycle ("one-carbon metabolism") plays a role inglaucoma. (It plays a role in almost everything happening in the humanbody, but we see specific connections to glaucoma.)

My hypothesis in regard to the selenium paradox is that the pathologicalrole of selenium in glaucoma is due to abnormalities in one-carbonmetabolism that must be present in a large porportion of glaucoma patientsbut that have so far not been characterized by researchers in this field.The evidence for this comes from *connecting the dots* from glaucomaresearch to research in other fields. The present paper is just that: anexercise in connecting the dots.

Future experimental research will have to be designed to test thishypothesis. The value of this paper is to stimulate thinking about thisparadox (as well as to make people aware that there is a paradox). I hopeit leads to deeper investigation of one-carbon metabolism in glaucoma.

On the basis of a better understanding of one-carbon metabolism inglaucoma, I expect to find more evidence that vitamins B9 (folate) and B12(cobalamin) play an important role in glaucoma management. Understandingthe selenium paradox takes us a step in that direction. It also helps usunify the findings about selenium, certain genetic polymorphisms, and thepotential of several other nutrients for treating glaucoma such ascarnitine, coenzyme Q10, glutathione, choline / citicoline, NAC(N-acetyl-cysteine), and more. For example, optimizing one carbonmetabolism is likely to be a better approach than simply taking glutathionesupplements or other antioxidants.

Let me provide some evidence in support of my hypothesis. One specificpiece of information that has not been discussed in glaucoma research sofar is the special role of selenium and folate (B9) together (termed an"interaction") in the methylation cycle ("one-carbon metabolism").

>From a 2003 Journal of Nutrition article, we know the following:

"Although both selenium and folate deficiency have been shown to causeglobal DNA hypomethylation and increased cancer susceptibility, thenutrients have different effects on one-carbon metabolism [9]."

In this study, selenium and folate strongly *interacted* (P < 0.0001) toinfluence one-carbon metabolism. The nature of this interaction is a key tounderstanding the selenium paradox in glaucoma.

The primary biochemical role of folate is "the transfer of one-carbonmoieties" [10] as part of the methylation cycle.

Folate functions in DNA synthesis and repair, and in methylation, byproviding methylene and formyl groups for the synthesis of thymidine andpurines and methyl groups for the synthesis of S-adenosylmethionine (SAM).SAM is the methyl donor for DNA methylation reactions. DNA methylation isan important epigenetic mechanism exerting control on gene expression [10].Folate deficiency can cause DNA hypomethylation [10]. Both selenium andfolate deficiency result in global DNA hypomethylation [10].

In addition, if folate is low, *selenium should be low as well* [9] toavoid more pathology.

Those research findings are *critical* to our understanding. I believe thatexplains selenium's general behavior in glaucoma. But glaucoma researchersare not yet aware of those findings. And no one has thought about theirimplications (connected the dots).

When folate and the methylation cycle are functioning normally, Ihypothesize that selenium will not be pathological. And this concept leadsto some therapeutic ideas for glaucoma.

In a 2004 study in the American Journal of Nutrition, the block in themethylation cycle and glutathione deficiency were found to be linked.Dietary supplements used to restore the methylation cycle to normaloperation (methylcobalamin, folinic acid and trimethylglycine) alsorestored the levels of reduced and oxidized glutathione [17].

My hypothesis is that when the methylation cycle is restored to normaloperation in glaucoma patients, normal levels of selenium supplementationwill no longer be pathological.

However, we can state this another way. The pathological role of seleniumin the glaucoma disease process is (hypothesized to be) a consequence ofimpaired methylation in the one carbon metabolism pathways.

When the methylation cycle is restored to normal operation in glaucomapatients many innate antioxidant systems, including glutathione, willreturn to normal.*Fixing one carbon metabolism could be the single most important step aglaucoma patient can take toward reducing abnormal levels of oxidativestress.*What does this say about the future direction of glaucoma treatments? Someresearchers have concluded that, "the modulation of apro-oxidant/antioxidant status might be a relevant target for glaucomaprevention and therapy." I agree, but I go one step further and suggestthat the methylation cycle is where we need to put our attention when itcomes to developing the next treatment for glaucoma. Getting themethylation cycle working will underpin the proper modulation ofpro-oxidant/antioxidant status of the patient. Without doing that, anytreatment will simply be a band-aid. Ideally, that treatment approach willbe nutrigenomic in character.

*References (and abstracts)*

*1. Relationship between glaucoma and selenium levels in plasma and aqueoushumour.*

Abstract

AIM:

The aim of the study was to compare selenium levels in plasma and aqueoushumour in subjects with and without primary open-angle glaucoma (POAG).

METHODS:

Forty-seven POAG cases and 54 controls in this case-control study wererecruited from surgery patients at the University Physician's OphthalmologyClinic in Tucson, Arizona, USA. Aqueous humour and plasma selenium weredetermined by high-performance liquid chromatography ion channel plasmamass spectrometry (HPLC ICP-MS). Potential confounders were assessed via aquestionnaire. Biological samples were collected and processed at surgeryand analysed for selenium content after collection was complete. Outcomemeasures included the odds of glaucoma in relationship to plasma selenium,aqueous humour selenium, and the ratio of levels of aqueous humour seleniumto plasma selenium.

RESULTS:

Tertile of selenium and its relationship to POAG was examined. Afteradjustment for common glaucoma risk factors, the odds of glaucoma in thehighest tertile of plasma selenium (OR = 11.3; p = 0.03) and the middletertile of aqueous humour selenium (OR = 0.06; p = 0.02) was significantlyassociated with glaucoma.

CONCLUSION:

Although a causal pathway cannot be inferred from our analysis, our data,added to that of others, suggest that the pathology is selenium-related.

DNA damage is related to a variety of degenerative diseases such as cancer,atherosclerosis and neurodegenerative diseases, depending on the tissueaffected. Increasing evidence indicates that reactive oxygen species (ROS)play a key role in the pathogenesis of primary open angle glaucoma (POAG),the main cause of irreversible blindness worldwide. Oxidative DNA damage issignificantly increased in the ocular epithelium regulating aqueous humoroutflow, i.e., the trabecular meshwork (TM), of glaucomatous patientscompared to controls. The pathogenic role of ROS in glaucoma is supportedby various experimental findings, including (a) resistance to aqueous humoroutflow is increased by hydrogen peroxide by inducing TM degeneration; (b)TM possesses remarkable antioxidant activities, mainly related tosuperoxide dismutase–catalase and glutathione pathways that are altered inglaucoma patients; and (c) intraocular-pressure increase and severity ofvisual-field defects in glaucoma patients parallel the amount of oxidativeDNA damage affecting TM. Vascular alterations, which are often associatedwith glaucoma, could contribute to the generation of oxidative damage.Oxidative stress, occurring not only in TM but also in retinal cells,appears to be involved in the neuronal cell death affecting the optic nervein POAG. The highlighting of the pathogenic role of ROS in POAG hasimplications for the prevention of this disease as indicated by the growingnumber of studies using genetic analyses to identify susceptibleindividuals and of clinical trials testing the efficacy of antioxidantdrugs for POAG management.Abbreviations

A significant increase in superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities was found in aqueous humor of POAG and PACGpatients as compared to cataract patients (p < 0.001). No significantchanges were observed in catalase activity. The levels of vitamins C and Ewere significantly lower in the aqueous humor of POAG and PACG as comparedto cataract patients (p < 0.001).

CONCLUSION:

These results suggest that a significant increase in oxidative stress mayplay a role in the pathogenesis of POAG and PACG. Determination ofoxidative stress in aqueous humor may help in understanding the course ofthis disease, and oxidative damage might be a relevant target for bothprevention and therapy.

Epidemiological evidence indicates that selenium supplementation mayincrease risk for glaucoma and ocular hypertension. The purpose of thisstudy was to determine the effects of selenium on trabecular meshworkcells, a likely site of pathology for glaucoma. Human trabecular meshwork(HTM) cells and human umbilical vein endothelial cells (HUVECs) weretreated with selenium (MSeA) at or near physiologically relevantconcentrations. Selenium uptake by cells was monitored using massspectrometry. Alterations in protein secretion, intracellular signaling,and cell morphology were monitored; and the role of integrin signaling inMSeA-induced morphological alterations was investigated using divalentcation treatments. Radiolabeling was used to assess protein synthesis andsecretion, while luciferase and MTT assays monitored total cellular ATP andcell viability, respectively. Whereas detectible changes in intracellularselenium were observed after exposure to 1-10 microM MSeA for 24hr, themajority remained in the conditioned medium. Selenium-induced morphologicalchanges (< or =3 hr) occurred before alterations in protein secretion andintracellular signaling (3-6 hr). Zinc treatment preventedselenium-mediated alterations in protein secretion and changes incell-matrix adhesion. MSeA treatment (5 microM) led to a 60% decrease inprotein synthesis after 3 hr and a 30% reduction in secretion, althoughsignificant alterations in cell viability and total ATP were not observedafter MSeA treatment. Selenium altered several indicators of HTM cellhomeostasis, but did not affect viability at physiologically relevantdoses. Similar results with HUVECs have implications for understandingselenium's mechanisms of action as an anti-angiogenic agent.

Several observations suggest a role for DNA methylation in cancerpathogenesis. Although both selenium and folate deficiency have been shownto cause global DNA hypomethylation and increased cancer susceptibility,the nutrients have different effects on one-carbon metabolism. Thus, thepurpose of this study was to investigate the interactive effects of dietaryselenium and folate. Weanling, Fischer-344 rats (n = 23/diet) were feddiets containing 0 or 2.0 mg selenium (as selenite)/kg and 0 or 2.0 mgfolate/kg in a 2 x 2 factorial design. After 3 and 4 wk of a 12-wkexperiment, 19 rats/diet were injected intraperitoneally withdimethylhydrazine (DMH, 25 mg/kg) and 4 rats/diet were administered saline.Selenium deficiency decreased (P < 0.05) colonic DNA methylation and theactivities of liver DNA methyltransferase and betaine homocysteinemethyltransferase and increased plasma glutathione concentrations. Folatedeficiency increased (P < 0.05) the number of aberrant crypts per aberrantcrypt foci, the concentration of colonic S-adenosylhomocysteine and theactivity of liver cystathionine synthase. Selenium and folate interacted (P< 0.0001) to influence one-carbon metabolism and cancer susceptibility suchthat the number of aberrant crypts and the concentrations of plasmahomocysteine and liver S-adenosylhomocysteine were the highest and theconcentrations of plasma folate and liver S-adenosylmethionine and theactivity of liver methionine synthase were the lowest in rats fedfolate-deficient diets and supplemental selenium. These results suggestthat selenium deprivation ameliorates some of the effects of folatedeficiency, probably by shunting the buildup of homocysteine (as a resultof folate deficiency) to glutathione.

*10. Relevance of folate metabolism in the pathogenesis of colorectalcancer.*

Abstract

The purpose of this review is to outline the principal mechanisms involvedin folate metabolism and how they may relate to the pathogenesis ofcolorectal cancer (CRC). In recent years, mild folate depletion (low normallevel) has been associated with an increased risk of developing certaincancers, in particular colorectal neoplasia. The epidemiologic andmechanistic evidence linking folate deficiency with carcinogenesis isreviewed, with a particular emphasis on colorectal neoplasia.Methylenetetrahydrofolate reductase (MTHFR) is a critical folatemetabolizing enzyme, and a functional polymorphic variant of this enzyme,the so-called thermolabile variant, caused by a C677T transition in theMTHFR gene, is common in the general population. This review criticallyexamines the evidence that suggests that carriers of this C677T variant maybe at increased risk of developing colorectal neoplasia. Although folatedepletion may predispose to the initiation of the neoplastic process,folate supplementation, on the other hand, might potentiate the progressionof an already established early neoplastic clone (eg, a colorectaladenoma). This could have potential public health implications, given anincreasingly widespread policy of folate supplementation of food staples.

To assess the level of plasma glutathione in patients with untreatedprimary open-angle glaucoma.

METHODS:

Twenty-one patients with newly diagnosed primary open-angle glaucoma and 34age- and gender-matched control subjects were subjected to a blood analysisto detect the level of circulating glutathione in its reduced and oxidizedforms. The effect of age, gender, and systemic blood pressure oncirculating glutathione levels was also analyzed.

Thirty patients with primary open-angle glaucoma and twenty-five patientswith senile cataracts of matched age and gender were included in the studyprospectively. Aqueous humor samples were obtained by paracentesis at thetime of elective surgery for glaucomatous and cataractous patients. Aqueoushumor were analyzed for CAT, GPO, SOD, and MDA status.

RESULTS:

GPO, SOD, and MDA enzyme levels revealed a high significant increase inaqueous humor of POAG patients with respect to the comparative group ofcataract patients (P < 0.001). No significant difference in the activity ofCAT enzyme in aqueous humor of POAG and cataract patient (P = 0.201).Significant correlation was found between the MDA enzyme level and severevisual field loss (P < 0.001) in POAG patients.

CONCLUSION:

Increased levels of aqueous humor GPO, SOD, and MDA may be associated withPOAG. In addition, they may be useful antioxidant enzyme levels in aqueoushumor of POAG patients as a result of glaucoma disease and not a cause.

Oxidative stress and antioxidant status in eye tissues may be associatedwith glaucomatous damage. The aim of this study was to establish theantioxidant status of aqueous humor of patients with primary open-angleglaucoma. For this purpose the authors measured the total reactiveantioxidant potential (TRAP) and the activities of the antioxidant enzymessuperoxide dismutase (SOD), catalase, and glutathione peroxidase.DESIGN:

Case control study.

METHODS:

Aqueous humor was obtained at the time of surgery from 24 patients withglaucoma and 24 cataract patients; TRAP was measured by chemiluminescence.Activities of the antioxidant enzymes were measured spectrophotometrically.Superoxide dismutase activity was determined by inhibition of the rate ofadrenochrome formation at 480 nm. Catalase activity was evaluated bydecrease of H(2)O(2) absorbance at 240 nm. Glutathione peroxidase (GPx)activity was determined following nicotinamide adenine dinucleotidephosphate oxidation at 340 nm.

RESULTS:

Total reactive antioxidant potential value of the cataract group was 124+/- 5 micromol/l Trolox. This value was significantly decreased, by 64%, inglaucoma patients. An increase of 57% in SOD activity was observed inglaucoma patients when compared with cataract patients (41.7 +/- 2.7 USOD/ml). Glutathione activity was threefold higher in glaucoma patientsthan in the cataract group (6.1 +/- 0.6 U/ml). No significant changes werefound in catalase levels.

CONCLUSIONS:

Oxidative stress may lead to an induction of antioxidant enzymes andcontribute to TRAP decrease. Superoxide dismutase, GPx activities, and TRAPmay be useful oxidative stress markers in aqueous humor of glaucomapatients.

Primary open-angle glaucoma (POAG) is the leading cause of blindness in theindustrial countries. It is reported that oxidative stress might be animportant risk factor in the pathogenesis of POAG. Forty subjects including20 patients with open-angle glaucoma (9 men and 12 women, mean age61.8±12.1yr) and 20 controls without glaucoma symptoms (9 men and 12 women,mean age 58.1±17.7yr) were enrolled in our study. The main aim of the workwas to evaluate oxidative stress markers in the pathogenesis of open-angleglaucoma. In our work the activity of antioxidant enzymes: catalase (CAT),superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as thetotal antioxidant status (TAS) was estimated. An alkaline comet assay wasused to measure DNA damage of strand breaks (SB), oxidized purines asglicosylo-formamido-glicosylase (Fpg) sites, and oxidized pirmidines asendonuclease III (Nth) sites. We measured endogenous as well as exogenousDNA damage after 10μM hydrogen peroxide treatment (H(2)O(2)). We did notobserve any statistical changes of DNA strand break lesion in examined POAGpatients according to healthy subjects (P>0.05). However, either endogenous(P<0.01) or exogenous (P<0.001) levels of oxidative DNA damage in POAGpatients were found to be statistically higher than controls. A significantdecrease of antioxidant enzymes: CAT (P<0.001), SOD (P<0.05), and GPX(P<0.001) and a non-statistical decrease of TAS status (P>0.05) in glaucomapatients according to controls were also indicated. In conclusion our datarevealed that oxidative stress had a pathogenic role in primary open-angleglaucoma. Therefore, we suggested that the modulation of apro-oxidant/antioxidant status might be a relevant target for glaucomaprevention and therapy.

*16. The ratio of oxidized/reduced glutathione as an index of oxidativestress in various experimental models of shock syndrome.*

Abstract

Red blood cells are well equipped to handle intracellular oxidative stress,their membranes are permeable to O2- and H2O2, and in this way they areimportant regulators of oxygen reactions occurring in their surroundings.The protective effect against reduced oxygen species - generated during theendothelial cell injury of various tissues - is attributed mainly to theglutathione metabolism of red blood cells. The blood concentration ofreduced (GSH) and oxidized glutathione (GSSG) was determined by a sensitivemethod using glutathione reductase in experimental shock syndromes inducedby paraquat toxicity, tourniquet ligature and endotoxin in rats, bybleeding and reperfusion in dogs and by transient ligature of thoracicaorta in newborn piglets. Under these conditions the concentration of GSSGwas elevated and GSH was lowered, resulting in an increase in the redoxratio: [GSSG/(GSH + GSSG)] x 100 (GSSG/GSH); particularly duringreperfusion. Determination of the GSSG/GSH seems to be a reliable index toassess the degree of oxidative stress "in vivo".

*17. Metabolic biomarkers of increased oxidative stress and impairedmethylation capacity in children with autism.*Abstract

BACKGROUND:

Autism is a complex neurodevelopmental disorder that usually presents inearly childhood and that is thought to be influenced by genetic andenvironmental factors. Although abnormal metabolism of methionine andhomocysteine has been associated with other neurologic diseases, thesepathways have not been evaluated in persons with autism.

OBJECTIVE:

The purpose of this study was to evaluate plasma concentrations ofmetabolites in the methionine transmethylation and transsulfurationpathways in children diagnosed with autism.

DESIGN:

Plasma concentrations of methionine, S-adenosylmethionine (SAM),S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine,cysteine, and oxidized and reduced glutathione were measured in 20 childrenwith autism and in 33 control children. On the basis of the abnormalmetabolic profile, a targeted nutritional intervention trial with folinicacid, betaine, and methylcobalamin was initiated in a subset of theautistic children.

RESULTS:

Relative to the control children, the children with autism hadsignificantly lower baseline plasma concentrations of methionine, SAM,homocysteine, cystathionine, cysteine, and total glutathione andsignificantly higher concentrations of SAH, adenosine, and oxidizedglutathione. This metabolic profile is consistent with impaired capacityfor methylation (significantly lower ratio of SAM to SAH) and increasedoxidative stress (significantly lower redox ratio of reduced glutathione tooxidized glutathione) in children with autism. The intervention trial waseffective in normalizing the metabolic imbalance in the autistic children.

CONCLUSIONS:

An increased vulnerability to oxidative stress and a decreased capacity formethylation may contribute to the development and clinical manifestation ofautism.

*18. Note:* Interestingly, while all studies I know of show low glutathionestatus in glaucoma patients, there is not an agreement among the studieswhen it comes to glutathione peroxidase, the enzyme that uses glutathione-- except to say that it's levels are not normal. I do not (yet) have anexplanation for that discrepancy. However, it does fit into the hypothesisthat restoring normal methylation cycle function will resolve theparadoxically pathological role of selenium in glaucoma.

*19. Oxidative stress markers in aqueous humor of glaucoma patients.*

Abstract

PURPOSE:

Oxidative stress and antioxidant status in eye tissues may be associatedwith glaucomatous damage. The aim of this study was to establish theantioxidant status of aqueous humor of patients with primary open-angleglaucoma. For this purpose the authors measured the total reactiveantioxidant potential (TRAP) and the activities of the antioxidant enzymessuperoxide dismutase (SOD), catalase, and glutathione peroxidase.

DESIGN:

Case control study.

METHODS:

Aqueous humor was obtained at the time of surgery from 24 patients withglaucoma and 24 cataract patients; TRAP was measured by chemiluminescence.Activities of the antioxidant enzymes were measured spectrophotometrically.Superoxide dismutase activity was determined by inhibition of the rate ofadrenochrome formation at 480 nm. Catalase activity was evaluated bydecrease of H(2)O(2) absorbance at 240 nm. Glutathione peroxidase (GPx)activity was determined following nicotinamide adenine dinucleotidephosphate oxidation at 340 nm.

RESULTS:

Total reactive antioxidant potential value of the cataract group was 124+/- 5 micromol/l Trolox. This value was significantly decreased, by 64%, inglaucoma patients. An increase of 57% in SOD activity was observed inglaucoma patients when compared with cataract patients (41.7 +/- 2.7 USOD/ml). Glutathione activity was threefold higher in glaucoma patientsthan in the cataract group (6.1 +/- 0.6 U/ml). No significant changes werefound in catalase levels.

CONCLUSIONS:

Oxidative stress may lead to an induction of antioxidant enzymes andcontribute to TRAP decrease. Superoxide dismutase, GPx activities, and TRAPmay be useful oxidative stress markers in aqueous humor of glaucomapatients.